The objective of the proposed study is to investigate the time course, reversibility and mechanism of the oligospermia, abnormal sperm morphology and defects in sperm function observed after heavy exposure to marihuana. Male rodents will be exposed by inhalation or by ingestion for 10 to 30 days to marihuana products of known cannabinoid concentration in doses approximating human consumption. Effect of such treatment of DNA, RNA and protein synthesis in the male gonad of the rodent during spermatogenesis and steroidogenesis will be studied. In Vitamin A deficient rats exposed to marihuana, the effect of the drug on transcriptional and morphological events during isolated stages of spermatogenesis (spermatogonial mitosis, meiosis and spermiogenesis) will be investigated. The relationship between hormonal levels and abnormalities of spermatogenesis in marihuana treated animals will be established. Growth, endocrine and gonodal function of offspring of the marihuana treated animal will be studied. The recovery of normal spermatogenesis (measured by sperm count, biochemistry of sperm function, spontaneous and stimulated motility, acrosin activity and DNA content of sperm) will be studied in carefully screened chronic marihuana users, whose semen shows oligospermia and deficient sperm function. These subjects will be maintained drug-free for two months in a controlled environment to ascertain the extent of reversibility.